The Old Order Amish of Lancaster County, Pennsylvania initially numbered in the hundreds, and are now a population of over 200. This population is a well-defined, genetically homogeneous Caucasian population with very large sibships, a high degree of consanguinity, and well documented genealogies. The goal of this study is to recruit and phenotypically characterize large multiplex pedigrees with noninsulin dependent diabetes mellitus (NIDDM) for a genome-wide search for susceptibility genes for this heterogeneous and polygenic disorder. To date, over a thousand subjects have been studied. These individuals are from 80 two- and three-generation families constituting one extended pedigree and over 2000 sib pairs. Of the first consecutive 258 subjects recruited, 16.2% had diabetes if they had a first degree relative with diabetes, compared to only 6.5% if there was no first degree relative with diabetes (RR 2.5; p</-0.01, 95% CI 1.2-5.0). Phenotypic characterization includes family and medical history, anthropometry (height, weight, waist, hip, fat mass), 75 gram oral glucose tolerance test, hemoglobin A1c, and lipids. During the current reporting period, 1640 insulins and 1036 leptins were analyzed to further characterize phenotypically these known serum markers of glucose metabolism. Several different types of parametric and nonparametric analyses including affected sib pairs and pedigree member pair analysis are in process. CORE LABORATORY ONLY; NO INPATIENT DAYS OR OUTPATIENT VISITS.